chr3-7740807-A-T

Variant names:

• chr3-7740807-A-T
• rs56173829
• NM_000844.4:c.*401A>T

Variant summary

Our verdict is Benign. The variant received -10 ACMG points: 0P and 10B. BP4_Moderate BS1 BS2

The NM_000844.4(GRM7):​c.*401A>T variant causes a 3 prime UTR change. The variant allele was found at a frequency of 0.0077 in 162,640 control chromosomes in the GnomAD database, including 10 homozygotes. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: 𝑓 0.0076 (9 hom., cov: 32)
  • Exomes 𝑓: 0.0095 (1 hom.)
• Consequence: GRM7 NM_000844.4 3_prime_UTR
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 5.01
• Publications: 5 publications found

Genes affected

GRM7 (HGNC:4599): (glutamate metabotropic receptor 7) L-glutamate is the major excitatory neurotransmitter in the central nervous system, and it activates both ionotropic and metabotropic glutamate receptors. Glutamatergic neurotransmission is involved in most aspects of normal brain function and can be perturbed in many neuropathologic conditions. The metabotropic glutamate receptors are a family of G protein-coupled receptors that have been divided into three groups on the basis of sequence homology, putative signal transduction mechanisms, and pharmacologic properties. Group I includes GRM1 and GRM5, and these receptors have been shown to activate phospholipase C. Group II includes GRM2 and GRM3, while Group III includes GRM4, GRM6, GRM7 and GRM8. Group II and III receptors are linked to the inhibition of the cyclic AMP cascade but differ in their agonist selectivities. Multiple transcript variants encoding different isoforms have been found for this gene. [provided by RefSeq, Jun 2009]

GRM7 Gene-Disease associations (from GenCC):

• neurodevelopmental disorder with seizures, hypotonia, and brain imaging abnormalities

  Inheritance: AR Classification: STRONG, MODERATE Submitted by: G2P, Labcorp Genetics (formerly Invitae), Ambry Genetics

ENSG00000270207 (HGNC:):

ACMG classification

Our verdict: Benign. The variant received -10 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.46).
• BS1: Variant frequency is greater than expected in population sas. GnomAd4 allele frequency = 0.00757 (1151/152052) while in subpopulation SAS AF = 0.0256 (123/4796). AF 95% confidence interval is 0.022. There are 9 homozygotes in GnomAd4. There are 596 alleles in the male GnomAd4 subpopulation. Median coverage is 32. This position passed quality control check.
• BS2: High Homozygotes in GnomAd4 at 9 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
GRM7	NM_000844.4	c.*401A>T		3_prime_UTR_variant	Exon 10 of 10	ENST00000357716.9	NP_000835.1
GRM7	NM_181874.3	c.*472A>T		3_prime_UTR_variant	Exon 11 of 11		NP_870989.1
GRM7	XM_017006272.2	c.*472A>T		3_prime_UTR_variant	Exon 11 of 11		XP_016861761.1
GRM7	XM_017006273.2	c.*401A>T		3_prime_UTR_variant	Exon 10 of 10		XP_016861762.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
GRM7	ENST00000357716.9	c.*401A>T		3_prime_UTR_variant	Exon 10 of 10	1	NM_000844.4	ENSP00000350348.4

Frequencies

GnomAD3 genomes AF: 0.00758 AC: 1152 AN: 151934 Hom.: 9 Cov.: 32

Gnomad AFR AF: 0.00189

Gnomad AMI AF: 0.00220

Gnomad AMR AF: 0.00427

Gnomad ASJ AF: 0.00634

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.0258

Gnomad FIN AF: 0.0171

Gnomad MID AF: 0.00316

Gnomad NFE AF: 0.00969

Gnomad OTH AF: 0.00960

GnomAD4 exome AF: 0.00954 AC: 101 AN: 10588 Hom.: 1 Cov.: 0 AF XY: 0.0102 AC XY: 56 AN XY: 5472

African (AFR) AF: 0.00204 AC: 1 AN: 490

American (AMR) AF: 0.00 AC: 0 AN: 284

Ashkenazi Jewish (ASJ) AF: 0.00448 AC: 2 AN: 446

East Asian (EAS) AF: 0.00 AC: 0 AN: 616

South Asian (SAS) AF: 0.0795 AC: 7 AN: 88

European-Finnish (FIN) AF: 0.0220 AC: 19 AN: 862

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 58

European-Non Finnish (NFE) AF: 0.00875 AC: 61 AN: 6972

Other (OTH) AF: 0.0142 AC: 11 AN: 772

GnomAD4 genome AF: 0.00757 AC: 1151 AN: 152052 Hom.: 9 Cov.: 32 AF XY: 0.00802 AC XY: 596 AN XY: 74308

African (AFR) AF: 0.00188 AC: 78 AN: 41480

American (AMR) AF: 0.00426 AC: 65 AN: 15256

Ashkenazi Jewish (ASJ) AF: 0.00634 AC: 22 AN: 3468

East Asian (EAS) AF: 0.00 AC: 0 AN: 5164

South Asian (SAS) AF: 0.0256 AC: 123 AN: 4796

European-Finnish (FIN) AF: 0.0171 AC: 181 AN: 10570

Middle Eastern (MID) AF: 0.00340 AC: 1 AN: 294

European-Non Finnish (NFE) AF: 0.00969 AC: 659 AN: 68008

Other (OTH) AF: 0.00950 AC: 20 AN: 2106

Alfa AF: 0.00102 Hom.: 0

Bravo AF: 0.00581

Asia WGS AF: 0.00693 AC: 24 AN: 3476

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.46
CADD	Benign	15
DANN	Benign	0.83
PhyloP100		5.0
Mutation Taster		=100/0	polymorphism

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.0		Details are displayed if max score is > 0.2

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Other links and lift over

dbSNP: rs56173829; hg19: chr3-7782494;